Binding in vitro of pipequaline (45319 RP) onto plasma proteins and blood cells in man

Abstract Serum binding of pipequaline, a new anxiolytic drug, was studied in vitro by equilibrium dialysis. The percent binding in serum is high, 96.3%, and remains constant within the range of therapeutic concentrations. Investigations performed on isolated proteins with a wide range of concentrations showed one site with a high affinity constant (K a = 450,000 M −1 ) for α 1 -acid glycoprotein and two sites with a lower affinity constant (K a = 58,000 M −1 ) for human serum albumin. Binding to lipoproteins was saturable, with an affinity constant of 22,000 ⩽ K a ⩽ 35,000 M −1 . Over the range of therapeutic concentrations, the ratio of pipequaline concentrations in serum and red blood cells remained constant (14.4%) and was shown to be dependent on the free fraction of pipequaline in serum.